State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.
Mol Cell Biochem. 2011 Nov;357(1-2):387-95. doi: 10.1007/s11010-011-0909-z. Epub 2011 Jun 11.
Cyclophilin A (CypA) is a member of peptidyl prolyl isomerases (PPIases), which catalyze the cis/trans isomerization of prolyl peptide bonds on the NH-terminal side of Pro residues in peptide chains. Altered expression of CypA has been reported in hepatocellular carcinoma (HCC), but the biological functions of CypA in HCC remain unknown. We found that the level of CypA expression correlated with the metastatic capability of two HCC cell lines, MHCC97-L and MHCC97-H. Stable expression of ectopic CypA in SK-Hep1 cells promotes cell adhesion, motility, chemotaxis, and in vivo lung metastasis, without affecting cell proliferation. We further analyzed microarray results to identify target genes controlled by CypA. Twenty-one genes related to metastasis were altered by CypA over-expression. A member of matrix metalloproteinase, MMP3, was identified by microarray analysis. The regulation of MMP3 and its homologue MMP9 by CypA were further confirmed by quantitative real-time RT-PCR and zymography assay. Taken together, our data suggest that CypA promotes HCC cell metastasis at least partially through up-regulation of MMP3 and MMP9.
亲环蛋白 A（CypA）是肽基脯氨酰顺反异构酶（PPIases）的成员，它催化肽链中 Pro 残基 NH 末端侧脯氨酸肽键的顺/反异构化。已经报道 CypA 在肝细胞癌（HCC）中的表达发生改变，但 CypA 在 HCC 中的生物学功能仍不清楚。我们发现 CypA 表达水平与两种 HCC 细胞系 MHCC97-L 和 MHCC97-H 的转移能力相关。在 SK-Hep1 细胞中稳定表达异位 CypA 可促进细胞黏附、运动、趋化性和体内肺转移，而不影响细胞增殖。我们进一步分析了微阵列结果，以鉴定 CypA 控制的靶基因。21 个与转移相关的基因被 CypA 过表达改变。基质金属蛋白酶 MMP3 是通过微阵列分析鉴定的。通过定量实时 RT-PCR 和酶谱分析进一步证实了 CypA 对 MMP3 和 MMP9 的调节。总之，我们的数据表明 CypA 通过上调 MMP3 和 MMP9 至少部分促进 HCC 细胞转移。
